Richard Lower (1631–1691) performed the first successful animal-to-animal transfusion in February 1665; previous to this he had years of failed attempts due to clotting in the tubes (Figure 1.1). Lower used a medium-sized dog and exsanguinated it until “its strength was nearly gone”, and then connected the cervical arteries of two large mastiffs to the jugular vein of the exsanguinated dog. The recipient in the experiment was “apparently oblivious to its hurts” and “soon began to fondle its master and to roll on the grass to clean itself of blood”, indicating his first successful attempt to use a blood transfusion as a form of resuscitation. While Lower’s report was published in 1666, Jean-Baptiste Denis (1635–1704) also claimed to have performed the first successful animal-to-animal transfusion; unfortunately, his report was delayed from publication for a year due to the imprisonment of the editor of the publication (Greenwalt 1997).

First animal-to-human transfusions

While similar uncertain claims to the first human transfusion have been made, Jean-Baptiste Denis is believed to have performed the first animal-to-human transfusions. He performed a transfusion of lamb blood to a 15-year-old child who was suffering from a persistent fever; the child was reported to have “a clear and smiling countenance” after the transfusion. Denis also performed a transfusion to the son of the Prime Minister of Sweden (Baron Bond), without successfully curing him, and to others without complications (Greenwalt 1997).

Lower, who had performed the first animal-to-animal transfusion, also performed an animal-to-human transfusion in 1667 to Arthur Coga, who was described as a “harmless lunatic” and “eccentric scholar” at Pembroke College. He received a transfusion from the artery of a sheep and was reported to have “found himself well” afterwards.

The most notable report of an animal-to-human transfusion was on 19 December 1667, when Denis treated a patient named Antoine Mauroy, a 34-year-old newlywed husband who ran away to Paris to spend time indulging in sensual pleasures (Figure 1.2). Denis thought that a transfusion of calf blood would help calm Mauroy’s urges due to the gentle nature of calves. The transfusion was reported to improve Mauroy’s issues, making him quieter. The procedure was repeated several days later, but that time Mauroy experienced burning in his arm, pain over his kidneys, and tightness in his chest. A day later, he exhibited bleeding from his nose and dark urine. This signifies the first report of a severe transfusion reaction, likely acute hemolysis. Mauroy’s wife insisted that Mauroy be treated a third time 2 months later when he was exhibiting similar behavior, but Mauroy did not comply. He died the following night without receiving the transfusion. Mauroy’s wife was bribed by Denis’ enemies to state that a transfusion killed her husband, leading to Denis’ trial for manslaughter, for which he was exonerated. Rumors suggest that Mauroy’s wife poisoned him with arsenic, although the truth is unknown (Farr 1980).

Because of Denis’ experiences in France, his enemies were able to instate the Edict of Châtelet, effectively banning transfusion practices in France. It is likely that the magistrates in Rome and the Royal Society also enacted similar bans, therefore while some experimental transfusions were performed in other parts of the world, advancements in transfusion medicine were halted for the next 150 years (Greenwalt 1997).

18th and 19th centuries

During the 18th century, the value of transfusions in patients with severe wounds and hemorrhage was revealed. In 1749, a member of the Faculty of Paris named Cantwell stated that transfusions should not be forbidden in desperate situations. In 1788, Michele Rosa published is findings that animals in severe shock required whole blood instead of serum for successful resuscitation.

During the 19th century, James Blundell (1790–1877), who had witnessed many women die from postpartum hemorrhage, performed experiments with animals in preparation for transfusions to his patients (Figure 1.3). He limited his patients receiving transfusions to those suffering from severe hemorrhage and applied the knowledge gained by John Leacock on the apparent harm of xenotransfusions (transfusion of blood from a different species), thus attempting human-to-human transfusions. While the archives are somewhat contradictory regarding the number of successful cases, records show that in 1829 Blundell was able to successfully save a 25-year-old woman with postpartum hemorrhage by transfusing blood from one of the surgical team members. The blood transfusion was performed with a brass syringe, although Blundell later developed an instrument called the “impellor”, a funnel-like apparatus that was used well into the late 19th century (Figure 1.4). While Blundell voiced his opinion against the transfusion of animal blood to human patients, the practice remained prevalent as transfusion therapy returned to medical practice. However, reports of transfusions were rare, likely due to the fact that blood clotting was a common limitation in performing transfusions (Greenwalt 1997).

Blood groups discovered

In the late 1800s there was significant work done by various physicians to study the effects of transfusions between different species. In 1874, Ponfick presented his findings of residues from lysed red blood cells (RBCs) in a patient who died after receiving a transfusion from a sheep. Ponfick also observed detrimental physical effects including respiratory distress, defecation, and convulsions, as well as post-mortem findings such as dilated hearts, pulmonary and serosal hemorrhage, enlarged and congested kidneys, and hemorrhage of the liver in dogs, cats, and rabbits receiving sheep blood. Ponfick also described the accumulation of hematin in the renal tubules of surviving animals that developed kidney insufficiency. Ponfick’s findings were consistent with Panum, Landois, and Euhlenberg’s findings suggesting that adverse outcomes could be seen with transfusions between different species, secondary to hemolysis, kidney injury, and hyperkalemia (Greenwalt 1997).

In the 1800s, human-to-human transfusions were performed with a reasonable degree of success, frequently without signs of adverse reactions. This is probably because ABO incompatibilities in the general Caucasian population were only anticipated in one-third (35.6%) of randomly paired individuals (Greenwalt 1997). Nevertheless, there were still significant numbers of human-to-human transfusions resulting in fatal complications, which could not be explained by the work of Ponfick and others investigating inter-species transfusions (Greenwalt 1997). It was not until Landsteiner demonstrated agglutination using the serum from healthy humans mixed with another human’s blood that the concept of blood groups (A, AB, B, and O) was established, which led to advancements in compatibility testing using assessments for agglutination (Landsteiner 1961). In 1910, von Dungern and Hirszfeld published a report on the inherited nature of blood groups; the practice of exclusively using O donors for transfusions began in the 1930s (Greenwalt 1997).

Advent of anticoagulation

The impellor was the tool designed by Blundell and used for transfusions until the 20th century. Another cannula device was devised by Crile in an effort to prevent blood clotting; it enabled the temporary joining of the recipient’s vein and donor’s artery, although it took significant surgical skill and strong donor will to accomplish this procedure. Other methods of transfusion included using paraffin to line the blood collection container, defibrinating the blood, and transfusing the non-clotted portion of blood (Greenwalt 1997).

Various anticoagulants were also studied in an effort to make the transfusion process more feasible, including the use of sodium phosphate by the well-known Braxton-Hicks, but none of his four patients receiving transfusions survived. Ammonium sulfate, sodium bicarbonate, sulfarsenol, ammonium oxalate, arsphenamine, sodium iodide, sodium sulfate, and hirudin (extracted from leeches) were all anticoagulant compounds investigated and reported by various physicians in the 19th and 20th centuries. In 1890, Nicolas Maurice Arthus reported that sodium citrate was able to permanently keep blood in liquid form, but it was not until 1915 that the invention of sodium citrate for blood transfusion was officially claimed. In 1955, Lewisohn was awarded the American Association of Blood Banks (AABB) Landsteiner Award for producing the first sodium citrate solution in a vial. Citrate was initially blamed as a cause of febrile non-hemolytic transfusion reactions, which were later determined to be the result of endotoxin from bacterial contamination (Greenwalt 1997).

Concept of blood banking

While blood mixed solely with 3.8% sodium citrate exhibited hemolysis after 1 week of storage, a mixture of blood, sodium citrate, and dextrose did not demonstrate hemolysis for 4 weeks. During World War I, Oswald H. Robertson established the first blood bank at the United States Army Base Hospital No.5 by using collection sets that were autoclaved and designed to collect up to 800 mL of blood into 160 mL of 3.8% sodium citrate. In 1937, an article written by Bernard Fantus at the Cook County Hospital in Chicago describes collecting 500 mL of blood into 70 mL of 2.5% sodium citrate into a chilled flask, then storing it under refrigeration at 4–6 °C. This became known as the first blood bank, which stored blood for 4–5 days (McCullough 2012).

While dextrose solutions were known to increase the storage time of RBCs, maintaining sterility was still an issue due to caramelizing of the dextrose solution during autoclaving of the collection system. In the 1940s, acid-citrate dextrose (ACD) solutions were developed; the addition of acidic forms of sodium citrate prevented caramelization, which allowed extension of storage of RBC products to 21 days (Greenwalt 1997).

As the potential storage time for RBCs increased, concerns regarding RBC metabolism during storage arose. It was already recognized that 2,3-diphosphoglycerate (2,3-DPG) was a substance present in RBCs, even though its role in oxygen binding was not yet elucidated. The level of 2,3-DPG was also observed to be lower in more acidic environments, leading to the development of citrate-phosphate-dextrose (CPD) solutions in 1947. These solutions raised the pH to 5.6 and the addition of phosphate resulted in better preservation of 2,3-DPG. By 1960, the introduction of additive solutions containing adenine increased the storage time (Nakao et al. 1960) and the RBC survival time was extended to 42 days (Simon et al. 1962). This vastly improved the ability to store RBCs instead of using fresh whole blood.

Plasma component use

The introduction of plasma component therapy occurred during World War II, mainly for the treatment of shock. Edwin J. Cohn and his colleagues developed the method of fractionation, thus enabling the use of human albumin and plasma as resuscitation fluids. Cohn’s methods continue to be used today, with some modifications (Greenwalt 1997).

Invention of plastic bags and component processing

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